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Hydroxytryptophan (5-)
5-Hydroxytryptophan or 5-HTP is a naturally-occurring amino acid, a precursor to the neurotransmitter serotonin and an intermediate in tryptophan metabolism. It is marketed in the United States and other countries as a dietary supplement for use as an antidepressant, appetite suppressant, and sleep aid. Metabolism 5-Hydroxytryptophan is decarboxylated to serotonin (5-hydroxytryptamine or 5-HT) by the enzyme aromatic-L-amino-acid decarboxylase with the help of Vitamin B6. This reaction occurs both in nervous tissue and in the liver.Bouchard S, Bousquet C, Roberge AG. Characteristics of dihydroxyphenylalanine/5-hydroxytryptophan decarboxylase activity in brain and liver of cat. J Neurochem. 1981 Sep;37(3):781-7. PMID 6974228 5-HTP crosses the blood-brain barrier, while 5-HT does not. Excess 5-HTP, especially when administered with Vitamin B6, is thought to be metabolized and excreted before reaching the brain. Pharmacology The psychoactive action of 5-HTP is thought to derive from its effect on serotonin synthesis in central nervous system tissue. It is believed that an artificially high supply of 5-HTP causes the brain's serotonin-producing neurons to increase production. Increased serotonin production then leads to increased serotonin release. Some doctors suggest that 5-HTP be administered with a peripheral decarboxylase inhibitor (PDI) such as carbidopa (and without Vitamin B6, see above) in order to prevent 5-HTP's metabolism in the liver, which can lead to elevated levels of serotonin in the bloodstream (and side effects which include vomiting, and potentially fibrosis of the heart).Usenet post by Steven B. Harris: "5-HTP + B6 = Trouble; Doc Harris Presents Green Banana Award" Research shows that co-administration with carbidopa greatly increases plasma 5-HTP levels. However, several studies have reported that 5-HTP is effective even without a PDI. http://www.mwilliamson.com/5htps.htm Other studies have indicated the risk of a scleroderma-like condition resulting from the combination of 5-HTP and carbidopa. 5-HTP as therapeutic supplement 5-HTP, which is found in minute amounts in certain foods like turkey and cheese , is often sold as an over-the-counter therapeutic supplement. In this case, it is usually sourced from the seeds of Griffonia simplicifolia. Production of 5-HTP as a supplement increased when a similar serotonin-altering supplement, L-tryptophan, was temporarily barred from sale in the United States by the FDA. 5-HTP in supplement form is typically sold in 50 mg or 100 mg gelatin capsules. Risks and Side Effects 5-HTP raises blood serotonin levels, and because of the risks associated with elevated levels it should only be taken under the advice of a medical professional (See Chronic diseases resulting from serotonin 5-HT2B overstimulation). For instance, elevated blood serotonin levels are associated with cardiac valve failure and acute or chronic pulmonary hypertension. Comprehensive clinical data on other side-effects of 5-HTP are not available. Nevertheless, some product marketers claim that it causes fewer side effects than traditional antidepressants. The basis for these claims are anecdotal and have not been verified scientifically. Side effects of 5-HTP may include nausea, constipation, gas, drowsiness, decreased sex drive, anxiety, numbness, paresthesia, breathing problems, palpitations, chest pain, hallucinations and insomnia. 5-HTP can also have adverse interactions with other natural and traditional drugs. http://www.wholehealthmd.com/refshelf/substances_view/1,1525,747,00.html Research It has been alleged that 5-HTP can be used to treat mental disorders such as depression. Unfortunately, the studies to date are incomplete. Reviews of these studies do indicate that potential exists for 5-HTP in the treatment of depression, but further trials are stressed as necessary before arriving at any firm conclusion.Altern Med Rev. 2000 Feb; 5(1), 64-71 [http://www.ncbi.nlm.nih.gov/entrez?cmd=retrieve&db=pubmed&list_uids=10696120 Use of neurotransmitter precursors for treatment of depression.], Meyers S. Similar deficits have been observed in long term/high dose psychostimulant users. Such deficits are especially apparent in those who have used amphetamine and methamphetamine. Amphetamines, and to a lesser extent cocaine, can damage serotonergic neurons in the CNS. Similar benefits have been seen in those with cognitive deficits resulting from psychostimulant use.Eur J Pharmacol. 2002 Jun 12;445(3):221-9. [http://www.ncbi.nlm.nih.gov/entrez?cmd=retrieve&db=pubmed&list_uids=12079687 Involvement of 5-hydroxytryptamine neuronal system in Delta(9)-tetrahydrocannabinol-induced impairment of spatial memory.], Egashira N, Mishima K, Katsurabayashi S, Yoshitake T, Matsumoto Y, Ishida J, Yamaguchi M, Iwasaki K, Fujiwara M. Current research shows promise in using 5-HTP for treating children with night terrors. After six months of use 83.9% of the children treated with 5-HTP were free from their persistent nightmares. Eur J Pediatr. 2004 Jul;163(7):402-7. Epub 2004 May 14. [http://www.ncbi.nlm.nih.gov/entrez?cmd=retrieve&db=pubmed&list_uids=15146330 L -5-Hydroxytryptophan treatment of sleep terrors in children], Bruni O, Ferri R, Miano S, Verrillo E. Some persons with fibromyalgia find that 5-HTP improves their symptoms.J Int Med Res. 1992 Apr;20(2):182-9 [http://www.ncbi.nlm.nih.gov/entrez?cmd=retrieve&db=pubmed&list_uids=1521674 Primary fibromyalgia syndrome and 5-hydroxy-L-tryptophan: a 90-day open study.], Sarzi Puttini P, Caruso I. Fibromyalgia sufferers report improvement in sleep, depression, pain and all major complaints related to fibromyalgia.J Int Med Res. 1990 May-Jun;18(3):201-9. [http://www.ncbi.nlm.nih.gov/entrez?cmd=retrieve&db=pubmed&list_uids=2193835 Double-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome.], Caruso I, Sarzi Puttini P, Cazzola M, Azzolini V. Studies are continuing to refine dosage and continued use. Uses In recent years 5-HTP has been sold by health food companies as an alternative treatment for depression and mood disorders. Its role as an intermediary in the biosynthesis of serotonin indicates that this chemical may indeed be effective in treating these and other serotonin-related disorders, but there is some debate on the conclusions of the clinical trials which have been carried out using the drug. It is also used as a prophylactic against chronic daily headache. 5-HTP may also be useful in treatment for migraines, since studies have shown that migraines occur when serotonin levels are low. 5-HTP is also used as a supplement by users of MDMA (commonly known as ecstasy) to help replenish depleted serotonin, in an attempt to alleviate to a degree the depression and overall mental unsettlement that sometimes occurs in the days following MDMA usage. 5-HTP is less commonly used immediately before the use of MDMA as a means to both further reduce the negative psychological effects of depleted serotonin, and as an attempt to boost the effects of MDMA. Some users report a moderate muting of the MDMA effect.MDMA and 5-HTP information and advice Dosage Though there is no official dosage, most supplement providers recommend 50 mg or 100 mg 5-HTP, one to three times per day. Most clinical studies have tested doses of 200-300 mg/day, although one study tested doses as large as 3250 mg/day. In many clinical studies 5-HTP is administered with carbidopa, which substantially changes 5-HTP's pharmacology. Although many studies do not report a dosing schedule, the majority of those that do have reported using two to four doses spaced throughout the day. The most effective timing would be before sleep, and on an empty stomach. Consumption with other proteins or amino acids will decrease absorption in the digestive tract. In theory, an overdose of 5-HTP could cause serotonin syndrome. However, serotonin syndrome was not observed in several studies that augmented traditional antidepressant therapy with 5-HTP, even though the combination therapy was expected to increase the risk of serotonin syndrome above 5-HTP alone. In dogs, doses of 23.6 mg/kg were found to cause toxic reactions, although the dose response curve for any animal with any drug will probably not scale to humans. Some users report high doses (300 mg and over) can produce nausea and vomiting. High doses may be damaging to the liver, due to the fact that the level of each amino acid in the blood must be tightly regulated by removal of any excess. See also *Serotonin *Tryptophan *Vitamin B6 *Pyridoxal Phosphate (PLP) - Bioactive form of vitamin B6 References Further reading *Information Paper on L-tryptophan and 5-hydroxy-L-tryptophan at Food and Drug Administration, February 2001 * * *article at Psychology Today * *Erowid L-tryptophan and 5-HTP Information Vault at Erowid *5-Hydroxytryptophan (5-HTP) Supplement Information at University of Maryland Medical Center *MDMA slideshow at DanceSafe Category:Neurotransmitters Category:Dietary supplements Category:Nootropics Category:Tryptophan